This document discusses how to interpret a forest plot used in a meta-analysis. A forest plot visually displays the results of individual studies and the overall meta-analysis. It shows the odds or risk ratio for each study with confidence intervals, along with a diamond representing the combined results. The location of the diamond in relation to the line of no effect indicates whether the overall effect is statistically significant. Heterogeneity between studies is also assessed using the forest plot and quantitative measures.

1. How to read a forest plot?
Samir Haffar M.D.
Assistant Professor of Gastroenterology

2. Clinical history
• 60-year-old man with acute biliary pancreatitis
• Ranson’s score: 4 – No fever – Normal WBCs
• CECT* on day 7: CT grading system of Balthazar 3
Necrosis score 2
CT severity index 5
• You wonder if prophylactic antibiotics prevents infection
of non-infected pancreatic necrosis & decreases mortality
*CECT: Contrast-Enhanced Computed Tomography

3. Ranson’s score for gallstone pancreatitis
Age > 70 yr
Blood glucose >220 mg/dl
WBC >18,000/mm3
LDH > 400 IU/L
ASAT > 250 IU/L
At presentation
1 point for each positive factor
Severe acute pancreatitis: ≥ 3
Ranson JHC. Am J Gastroenterol 1982;77:633.
During initial 48 hr
Ht >10% decrease
Serum calcium < 8 mg/dl
Base deficit > 5 mEq/L
BUN > 2 mg/dl increase
Fluid sequestration > 4 L

4. CT grading system of Balthazar
Grade Description Points
A Normal pancreas 0
Balthazar EJ et al. Radiology 1990 ; 174 : 331 – 6.
B Pancreatic enlargement 1
C Inflammation of pancreas or peripancreatic fat 2
D Single peripancreatic fluid collection 3
E ≥ 2 fluid collections or retroperitoneal air 4

5. Necrosis score
Necrosis Points
No pancreatic necrosis 0 points
One third of pancreas 2 points
One half of pancreas 4 points
> one half of pancreas 6 points

6. CT severity index
The index ranges from 0 to 10
Severe acute pancreatitis ≥ 3
CT grading of Balthazar
(0 – 4 points)
Necrosis score
(0 – 6 points)
+
Morgan DE. Clin Gastroenterol Hepatol 2008 ; 6 : 1077 – 1085.

7. CT Severity Index (CTSI)
Localized fluid collection adjacent to tail: CT grading (3 points)
Lack of enhancement of pancreatic tail: Necrosis <30 % (2 points)
Absence of retroperitoneal air

9. Bai Y et al. Am J Gastroenterol 2008 ; 103 : 104 – 110.
Antibiotic prophylactic in pancreatic necrosis
Flow diagram

10. Characteristics of RCTs included in MA
Bai Yu & al. Am J Gastroenterol 2008 ; 103 : 104 – 110.
467 patients included in 7 trials

11. Data analysis
2 stage statistical process of MA
Statistical power of MA is often very high
• Treatment effect for each study
p value (p)
Relative Risk (RR) or Odds Ratio (OR)
Confidence Intervals (CIs)
Number Needed to Treat (NNT)
• Overall treatment effect
Calculated as weighted average of individual statistics

12. • p > 0.05 Statistically insignificant
• p < 0.05 Statistically significant
Probability value (p value)
Statistically
significant
Clinically
significant
Doesn't
mean

13. Risk & Odds
Risk
a
a + b
Risk =
RR: risk patients/risk controls
Odds
a
b
Odds =
OR: odds patients/odds controls

14. Interpretation of RR & OR
OR or RR should be accompanied by CI
RR or OR > 1
Increased likelihood of outcome in treatment group
RR or OR < 1
Decreased likelihood of outcome in treatment group
RR or OR = 1
No difference of outcome between tt & control group

15. Confidence Intervals
Value 95 % CI are commonly used
90 or 99% CI are sometimes used
Width of CI Indicates precision of the estimate
Wider the interval, less the precision
CI includes 1 No statistically significant difference
CI doesn’t include 1 Statistically significant difference

16. Statistical significance & CI
(a) Statistically significant , low precision
(b) Statistically significant, high precision
(c) Not statistically significant, low precision
(d) Not statistically significant, high precision
Glasziou P et al. Evidence based practice workbook. Blackwell, 2nd edition, 2007.

17. Number Needed to Treat (NNT)
• Relative risk (RR)
Risk in treatment group / risk in control group
• Absolute risk reduction (ARR)
Risk in control group – risk in treatment group
• NNT (expressed in clinically relevant way)
1 /ARR

18. Statistical methods/overall treatment effect
Larger trials have more influence than smaller ones
Fixed effects model 1
Random effects model 2
Bayesian models3 Controversial
Fixed & random effects
1 Prog Cardiovasc Dis 1985 ; 17 : 335 – 71.
2 Stat Med 1992 ; 11 : 141 – 58.
3 BMJ 1996 ; 313 : 603 – 7.
No single
correct method

19. Reporting the results
The typical graph for displaying results
of a meta-analysis is called a ‘‘forest plot’’

20. Antibiotic prophylaxis & prevention of infection
Bai Y et al. Am J Gastroenterol 2008 ; 103 : 104 – 110.
Forest plot

21. Bai Y et al. Am J Gastroenterol 2008 ; 103 : 104 – 110.
Antibiotic prophylaxis & & prevention of infection
Horizontal line
Scale measuring the treatment effect

22. Bai Y et al. Am J Gastroenterol 2008 ; 103 : 104 – 110.
Antibiotic prophylaxis & infected necrosis
Vertical line or line of no effect
Treatment & control groups have the same effect

23. Antibiotic prophylaxis & infected necrosis
Bai Y et al. Am J Gastroenterol 2008 ; 103 : 104 – 110.
Point estimate & CIs for each study

24. Point estimate (RR or OR) & CI
Gallin JI, Ognibene FP. Principles & practice of clinical research.
A Press, 2nd ed, 2005.

25. Antibiotic prophylaxis & infected necrosis
Bai Y et al. Am J Gastroenterol 2008 ; 103 : 104 – 110.
Diamond

26. The diamond
Perera R, Heneghan C, Badenoch D. Statistics Toolkit.
Blackwell Publishing Ltd, Oxford, 1st edition, 2008.
Shows combined point estimate (OR or RR)
& CI for the meta-analysis

27. Diamond in meta-analysis
Diamond on Left of the line of no effect
Less episodes of outcome of interest in treatment group
Diamond on Right of the line of no effect
MoRe episodes of outcome in treatment group
Diamond touches the line of no effect
No statistically significant difference between groups
Diamond does not touch the line of no effect
Difference between two groups statistically significant

28. Bai Y et al. Am J Gastroenterol 2008 ; 103 : 104 – 110.
Antibiotic prophylaxis & infected necrosis
The diamond
Shows the overall result of MA

29. Effect of antibiotic prophylaxis on mortality
Bai Y et al. Am J Gastroenterol 2008 ; 103 : 104 – 110.
The diamond

30. Interpretation of forest plot
Names on left First authors of primary studies
Black squares RR or OR of individual studies
Black square size Weight of each trial in MA
Horizontal lines 95% confidence intervals
Vertical line Line of no effect (OR or RR = 1)
Diamond Overall treatment effect
Diamond Center Combined treatment effect
Tips of diamond 95% CI

31. Relative Risk or Odds Ratio?
HP eradication in nonulcer dyspepsia
It is useful to analyze data in both OR & RR
Moayyedi P. Am J Gastroenterol 2004; : 2297-2301.
Using OR Using RR
Significant heterogeneity Reduced heterogeneity

32. Random or fixed effect modelS?
Prokinetics in nonulcer dyspepsia
Moayyedi P. Am J Gastroenterol 2004; : 2297-2301.
Small trials given more weight than large trials in random effects
Increase estimated overall effect size & widen the 95% CI
Random effects modelFixed effects model

33. Do the pieces fit together?
Heterogeneity
Simon SD. Statistical evidence in medical trials: What do the data really tell us?
Oxford University Press, Oxford, 1st edition, 2006

34. Measurement of heterogeneity in MA?
• Qualitative
Forest plot Visual evidence of heterogeneity
Funnel plot Visual evidence of heterogeneity
• Quantitative
X-squared
I-squared Based on Cochran’s Q
Simon SD. Statistical evidence in medical trials: What do the data really tell us?
Oxford University Press, Oxford, 1st edition, 2006

35. Heterogeneity & forest plot
Hypothetical MA
Some trials with lower C.I. above upper C.I. of other trials
Some lines do not overlap
McGovern D, Summerskill W, Valori R, Levi M. Key topics in EBM.
BIOS Scientific Publishers, 1st Edition, Oxford, 2001.

36. Funnel plots
Bias detected by simple graphical test
• Plot for each trial RR or OR on x axis
Sample size on y axis
• Absence of bias
Plot should resemble inverted funnel or Christmas tree
• Presence of bias
Plot shows asymmetrical & skewed shape

37. Ideal funnel plot
The smaller the trial, the larger the distribution of results
Cleophas TJ et all. Statistics applied to clinical trials.
Springer, The Netherlands , 3rd edition, 2006.

38. Cut Christmas tree
Cleophas TJ et all. Statistics applied to clinical trials.
Springer, The Netherlands , 3rd edition, 2006.
Negative trials not published (missing)
Suspicion of considerable publication bias in this MA

39. Funnel plot
Publication bias of antibiotics for infected necrosis
Bai Y et al. Am J Gastroenterol 2008 ; 103 : 104 – 110.

40. Funnel plot
Publication bias of trials of antibiotics for mortality
Bai Y et al. Am J Gastroenterol 2008 ; 103 : 104 – 110.

41. Quantitative measure of heterogeneity
Many prefer not to use quantitative measure
• X-squared:
Degree of freedom (df) Number of trials in MA – 1
X2 ≈ df No heterogeneity
X2 much greater than df Serious heterogeneity
• I-squared (0 – 100%)
< 25% No heterogeneity
50% – 75% Serious heterogeneity
Simon SD. Statistical evidence in medical trials: What do the data really tell us?
Oxford University Press, Oxford, 1st edition, 2006

42. Bai Y et al. Am J Gastroenterol 2008 ; 103 : 104 – 110.
Antibiotic prophylaxis & pancreatic necrosis
Heterogeneity
X2 = 7.82 (df 6 – No heterogeneity)
I2 = 23.2% (No or little heterogeneity)

43. Antibiotic prophylactic effect on mortality
Heterogeneity
Bai Y et al. Am J Gastroenterol 2008 ; 103 : 104 – 110.
X2 = 4.66 (df 6 – No heterogeneity)
I2 = 0 % (No or little heterogeneity)

44. Thank You